Circ_0039411通过介导miR-423-5p/SOX4信号通路促进甲状腺乳头状癌的发展。

IF 2.3 4区 医学 Q3 BIOTECHNOLOGY & APPLIED MICROBIOLOGY
Xiaohui Wen, Jingyan Du, Xun Wang
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引用次数: 7

摘要

背景:甲状腺乳头状癌是甲状腺癌最常见的组织学亚型,发病率高。我们旨在探讨环状RNA_0039411 (circ_0039411)在甲状腺乳头状癌进展中的功能及其相关机制。方法:采用逆转录-定量聚合酶链反应(RT-qPCR)和Western blot法分别检测RNA和蛋白的表达。通过集落形成实验、transwell迁移实验、transwell侵袭实验和流式细胞术分析细胞的集落形成能力、迁移、侵袭和凋亡。采用荧光葡萄糖测定试剂盒和荧光乳酸测定试剂盒分析细胞糖酵解代谢。采用双荧光素酶报告基因法和RNA-Pull-Down法验证microRNA-423-5p (miR-423-5p)与circ_0039411或SRY-box转录因子4 (SOX4)的结合。采用异种移植肿瘤模型评估circ_0039411在体内肿瘤生长中的作用。结果:Circ_0039411在甲状腺乳头状癌组织和细胞系中表达高于邻近正常组织和NTHY-ORI3.1细胞。Circ_0039411干扰抑制了甲状腺乳头状癌细胞的集落形成能力、迁移、侵袭能力和糖酵解能力,但促进了甲状腺乳头状癌细胞的凋亡。MiR-423-5p是circ_0039411在甲状腺乳头状癌细胞中的靶标。Circ_0039411敲低介导在甲状腺乳头状癌细胞中的作用在很大程度上被miR-423-5p的沉默所推翻。MiR-423-5p结合到SOX4的3'非翻译区(3' utr)。SOX4过表达在很大程度上逆转了circ_0039411沉默介导的甲状腺乳头状癌细胞效应。Circ_0039411通过海绵miR-423-5p在甲状腺乳头状癌细胞中正向调节SOX4的表达。Circ_0039411沉默在体内显著抑制异种移植物肿瘤的生长。结论:Circ_0039411促进甲状腺乳头状癌细胞的恶性行为,部分依赖于miR-423-5p/SOX4轴的调控。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Circ_0039411 promotes papillary thyroid carcinoma development through mediating the miR-423-5p/SOX4 signaling.

Background: Papillary thyroid carcinoma is the most frequent histological subtype of thyroid cancer with a high incidence. We aimed to explore the function of circular RNA_0039411 (circ_0039411) and its associated mechanism in papillary thyroid carcinoma progression.

Methods: Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and Western blot assay were conducted to determine the expression of RNA and protein, respectively. The colony formation ability, migration, invasion, and apoptosis were analyzed by colony formation assay, transwell migration assay, transwell invasion assay, and flow cytometry. Cell glycolytic metabolism was analyzed using fluorescence-based glucose assay kit and fluorescence-based lactate assay kit. Dual-luciferase reporter assay and RNA-Pull-Down Assay were performed to validate the binding between microRNA-423-5p (miR-423-5p) and circ_0039411 or SRY-box transcription factor 4 (SOX4). The xenograft tumor model was used to assess the role of circ_0039411 in the tumor growth in vivo.

Results: Circ_0039411 was highly expressed in papillary thyroid carcinoma tissues and cell lines compared with adjacent normal tissues and NTHY-ORI3.1 cells. Circ_0039411 interference suppressed the colony formation ability, migration, invasion, and glycolysis but promoted the apoptosis of papillary thyroid carcinoma cells. MiR-423-5p was a target of circ_0039411 in papillary thyroid carcinoma cells. Circ_0039411 knockdown-mediated effects in papillary thyroid carcinoma cells were largely overturned by the silence of miR-423-5p. MiR-423-5p bound to the 3' untranslated region (3'UTR) of SOX4. SOX4 overexpression largely reversed circ_0039411 silencing-mediated effects in papillary thyroid carcinoma cells. Circ_0039411 positively regulated SOX4 expression by sponging miR-423-5p in papillary thyroid carcinoma cells. Circ_0039411 silencing notably suppressed the growth of xenograft tumors in vivo.

Conclusion: Circ_0039411 promoted the malignant behaviors of papillary thyroid carcinoma cells partly depending on the regulation of the miR-423-5p/SOX4 axis.

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来源期刊
International Journal of Biological Markers
International Journal of Biological Markers 医学-生物工程与应用微生物
CiteScore
4.10
自引率
0.00%
发文量
43
期刊介绍: IJBM is an international, online only, peer-reviewed Journal, which publishes original research and critical reviews primarily focused on cancer biomarkers. IJBM targets advanced topics regarding the application of biomarkers in oncology and is dedicated to solid tumors in adult subjects. The clinical scenarios of interests are screening and early diagnosis of cancer, prognostic assessment, prediction of the response to and monitoring of treatment.
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